James M. Byers

Lidocaine elimination: Effects of metoprolol and of propranolol

The effects of administration of metoprolol and propranolol on lidocaine elimination were studied in six healthy young men who did not smoke. Each received three single intravenous doses of lidocaine (2.5 to 3.0 mg/kg injected over 10 min): one alone, one after 1 day pretreatment with propranolol (40 mg orally every 6 hr), and one after 1 day pretreatment with metoprolol (50 mg orally every 6 hr). Lidocaine clearance was 0.88 ± 0.28 l · hr−1 · kg−1 before beta blockade, 0.61 ± 0.20 l · hr−1 · kg−1 during metoprolol dosing, and 0.47 ± 0.16 l · hr−1 · kg−1 during propranolol dosing. There was no correlation between the change in lidocaine elimination and the steady‐state concentrations of metoprolol or propranolol, nor between the change in lidocaine clearance and the change in resting heart rate produced by either beta blocker. Metoprolol and propranolol reduce lidocaine elimination significantly.

Phenobarbital Pharmacokinetics and Bioavailability in Adults

Abstract: The pharmacokinetics and bioavailability of phenobarbital were examined in six healthy adult subjects after a 2.6 mg/kg intravenous and a 2.9 mg/kg oral dose. Serum concentrations of phenobarbital were followed by means of a high pressure liquid chromatographic assay for 21 days after drug administration. After the intravenous dose, the mean distribution half‐life was 0.18 hour and the mean elimination half‐life was 5.8 days. Mean total body clearance and mean renal clearance were 3.0 ml/hr/kg and 0.8 ml/hr/kg, respectively. The apparent volume of distribution was 0.60 liter/kg. After administration of phenobarbital tablets, the maximum phenobarbital serum concentration was 5.5 mg/liter at 2.3 hours after the dose. Adjusted absolute availability of phenobarbital from the tablets studied was 94.9 per cent (range 81–111.9 per cent). The elimination half‐life averaged 5.1 days for the oral dose. There was no evidence of autoinduction of phenobarbital elimination over the study period.

Cocaine-related deaths in Pima County, Arizona, 1982-1984

A three-year review of toxicology data from medical examiner autopsies in Pima County, Arizona, has demonstrated that cocaine has rapidly become a leading substance of abuse, second only to alcohol in the frequency of drugs detected by toxicologic analysis of all suspicious deaths, motor vehicle accident fatalities, homicides, and suicides. Gastric contents and urine were analyzed by thin-layer chromatography, and nasal swabs, blood, and urine were tested for the combination of cocaine and its metabolite benzoylecgonine by quantitative radioimmunoassay. A total of seventy-two deaths in Pima County from 1982 to 1984 have involved cocaine. Seventy percent of these have occurred in the last fifteen months. Marked variation in the individual response to cocaine compared to the blood concentration of cocaine/metabolite was noted.

Characterization of antigen-enzyme conjugates: Theoretical considerations for rate nephelometric assays of immunological reactivities

Abstract A simple method has been developed to assay the immunological reactivity of antigen-enzyme conjugates by rate nephelometry. Unlike immunodiffusion or immunoelectrophoresis, the procedure is independent of molecular hydrodynamics and is based on precipitin rate curves obtained by light-scattering measurements. To our knowledge, no such methods have yet been described in the literature to characterize these conjugates. Theoretical considerations indicate that the scattering properties of the precipitin particles obey Raleigh-Debye conditions. Thus, the rate of increase in light scatter measured is directly proportional to an increasing number of scattering centers on large, growing precipitin particles. This independence of the rate of change in light scatter from the absolute size of the particles makes rate nephelometry an ideal technique to quantitate immunological reactivity. This paper deals with a special case of the fundamental rate law that reoates the rate of change of light scatter to the antibody-antigen reaction under Rayleigh-Debye conditions. In addition, data for two types of conjugates which illustrate the validity of the technique are presented.

An Analysis of Toxic Deaths, 1982 to 1985, Pima County, Arizona

Toxic deaths in Pima County, Arizona, were studied over a four-year period. The deaths were analyzed according to cause and manner of death, toxic substance, and demographic data. The age group 40 to 49 years had the highest rate of suicide from toxic substances. The accident death rate was highest for ages 20 to 29 years. Carbon monoxide was most often found to be the cause of deaths in this study. The most prevalent drugs were narcotics followed by antidepressants, cocaine, and barbiturates. Comparisons are made with similar studies.

Cost Effective Drug Screening in the Laboratory

In the treatment of sudden, severe, often life-threatening toxic manifestations caused by exogenous substances, the laboratory plays a vital part. In its role in detecting, and if necessary, quantitating certain of these substances, the laboratory serves to support the hospital emergency room and intensive care units. This paper is intended to answer a number of questions relating to the effective use of laboratory services while simultaneously recognizing the cost constraints imposed upon the laboratory and the competition between other areas in the laboratory and elsewhere in the hospital for the constantly diminishing health care dollars. This paper will provide an overview of toxic substances seen in patients specimens examined by the laboratory and of the specific information which must be provided to the clinician by the laboratory. It will also discuss the funding for these services and the need for a new perspective in justifying the maintenance of such services. In this presentation certain considerations will be discussed. They are:

Trauma in patients influenced by drugs and alcohol

To examine the relationship of drugs, alcohol, and trauma, we conducted a retrospective study of 66,099 patients seen in the emergency department at the University of Arizona Health Sciences Center from August 1975 to July 1978. Of 646 patients found to have acute drug intoxication, 33 (5.1%) had sustained traumatic injury. Examination of blood, urine, and gastric specimens revealed only alcohol present in 17 (49%) of these patients. No specific pattern of drug ingestion or injury was seen in the remaining patients. While no generalizations can be made regarding prevention, the data may sensitize the clinician to the complex interrelationship of drugs, alcohol, and trauma.

Nutrition curriculum in medical education: An integrated and comprehensive approach

Background: In 1992 The University of Arizona, College of Medicine was awarded support from the NIH to develop an integrated, comprehensive nutrition curriculum for pre‐doctorate education. Historically 35 hr of nutrition instruction were provided, including 9 of 40 essential nutrition topics identified by the American Society of Clinical Nutrition. Description: To meet the need for an expanded curriculum, course materials were revised and new materials were developed to provide 36 of the essential topics and 20 new topics in 75 hours of nutrition education. Evaluation: Change in student nutrition knowledge is currently being evaluated. Early analysis supports improvements in scores on a written nutrition examination and the objective structured clinical examination. Comparison scores of the same students over time will be available in late 1997. Conclusion: Effective curricula which provide appropriate quality and quantity of medical nutrition information can be developed within current medical education...

Acetaminophen assay: the clinical consequences of a colorimetric vs a high-pressure liquid chromatography determination in the assessment of two potentially poisoned patients.

Following acetaminophen (APAP) overdosage, plasma half-life of APAP elimination appears to be a good prognostic indicator of potential hepatic toxicity. A half-life of greater than 4 hr is often associated with liver injury. In two patients who each allegedly ingested greater than 13 gm of APAP, serial assay procedures were performed using both a colorimetric (nitrous acid chromophore) method and HPLC for all samples. The data obtained were used to determine the plasma half life. A comparison of the results obtained from both methods revealed a significant variation. It appears that the colorimetric method, at lower plasma concentrations of APAP (less than 50 microgram/ml), overestimates the actual drug concentration, resulting in the calculation of a falsely prolonged plasma half-life. This may result in the unnecessary implementation of antidotal therapy. The HPLC method is considered to be more specific than the colorimetric analysis and to better reflect actual plasma APAP concentrations, especially at lower concentrations of APAP.